Natural Product: NPC73656

Natural Product IDNPC73656
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Riccardi C
IUPAC Name n.a.
Synonyms Riccardi C; Riccardin C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL411317
PubChem CID 10070992
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey JMKSVONWZFVEAI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C28H24O4/c29-22-9-13-24-21(17-22)8-3-18-4-10-23(11-5-18)32-28-16-20(7-14-26(28)30)2-1-19-6-12-25(24)27(31)15-19/h4-7,9-17,29-31H,1-3,8H2
SMILES Oc1ccc2c(c1)CCc1ccc(cc1)Oc1cc(CCc3ccc2c(O)c3)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.17 Volume:   453.585
?
Van der Waals volume.
Dense:   0.935 LogP:   3.979
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.336
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.659
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   33.0
TPSA:   69.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   8.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.317 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.61 Fsp3:   0.143
MCE-18:   58.5
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   1.0 Fluc inhibitor:   0.745
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.801
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.513
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.566 Promiscuous compounds:   0.149

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.789 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.104 Pgp-substrate:   0.099
PAMPA:   0.465
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.003
20% Bioavailability (F20%):   0.833 30% Bioavailability (F30%):   0.822
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.215 MRP1:   0.59
Plasma Protein Binding (PPB):   98.342% Volume Distribution (VD):   0.357
Fu: 0.822%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.928
OATP1B3 inhibitor:   0.958 BCRP inhibitor:   0.041
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.6 CYP1A2-substrate:   0.85
CYP2C19-inhibitor:   0.699 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.333
CYP3A4-inhibitor:   0.782 CYP3A4-substrate:   0.975
CYP2B6-substrate:   0.195 CYP2C8-inhibitor:   1.0
HLM stability:   0.989
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  6.196 Half-life (T1/2):  1.017

ADMET: Toxicity

hERG Blockers:  0.365 hERG Blockers (10um):  0.786
Human Hepatotoxicity (H-HT):  0.556 Drug-induced Liver Injury (DILI):  0.095
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.452
Maximum Recommended Daily Dose:  0.776 Skin Sensitization:  0.81
Carcinogencity:  0.589 Eye Corrosion:  0.0
Eye Irritation:  0.828 Respiratory Toxicity:  0.803
Drug-induced Neurotoxicity:  0.3 Ototoxicity:  0.467
Hematotoxicity:  0.105 Drug-induced Nephrotoxicity:  0.217
Genotoxicity:  0.801 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.761 Hek293 Cytotoxicity:  0.894
BCF:   1.709
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   5.212
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.455
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.316
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO33046 liverworts n.a. n.a. n.a. n.a. n.a. n.a. PMID[16378374]
NPO19581 Marchantia polymorpha Species Marchantiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO12644 Lunularia cruciata Species Lunulariaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO33046 liverworts n.a. n.a. n.a. n.a. n.a. n.a. PMID[21652215]
NPO12644 Lunularia cruciata Species Lunulariaceae Eukaryota n.a. n.a. n.a. PMID[30848895]
NPO19581 Marchantia polymorpha Species Marchantiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33046 liverworts n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO12644 Lunularia cruciata Species Lunulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19581 Marchantia polymorpha Species Marchantiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19581 Marchantia polymorpha Species Marchantiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12644 Lunularia cruciata Species Lunulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19581 Marchantia polymorpha Species Marchantiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1794 Individual protein LXR-alpha Homo sapiens IC50 = 4900.0 nM PMID[18343126]
NPT1746 Individual protein LXR-beta Homo sapiens IC50 = 6600.0 nM PMID[18343126]
NPT1794 Individual protein LXR-alpha Homo sapiens FC = 15.0 n.a. PMID[19103488]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 > 100000.0 nM PMID[16378374]
NPT306 Cell line PC-3 Homo sapiens IC50 = 3220.0 nM DOI[10.1039/C2MD20199B]
NPT306 Cell line PC-3 Homo sapiens Activity = 6.21 % DOI[10.1039/C2MD20199B]
NPT171 Cell line MRC5 Homo sapiens IC50 = 15000.0 nM PMID[30848895]
NPT81 Cell line A549 Homo sapiens IC50 = 22500.0 nM PMID[30848895]
NPT177 Tissue Aorta Rattus norvegicus Inhibition > 60.0 % PMID[21652215]
NPT20 Organism Candida albicans Candida albicans MIC = 8.0 ug.mL-1 PMID[29019405]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 3.2 ug.mL-1 PMID[23122868]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 2.0 ug.mL-1 PMID[26995530]
NPT28800 Protein family Cyclooxygenase Homo sapiens IC50 = 53500.0 nM PMID[29019405]
NPT2 Others Unspecified n.a. IC50 = 9900.0 nM PMID[18343126]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC73656 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7931 Intermediate Similarity NPC175453
0.7833 Intermediate Similarity NPC141023
0.75 Intermediate Similarity NPC606516
0.7377 Intermediate Similarity NPC189482
0.7213 Intermediate Similarity NPC599974
0.7143 Intermediate Similarity NPC483728
0.6875 Remote Similarity NPC601376
0.6607 Remote Similarity NPC5948
0.6349 Remote Similarity NPC483726
0.5965 Remote Similarity NPC299180
0.5873 Remote Similarity NPC17837
0.5738 Remote Similarity NPC599909
0.5738 Remote Similarity NPC604545
0.5714 Remote Similarity NPC55947
0.5636 Remote Similarity NPC86947
0.5507 Remote Similarity NPC99694
0.5373 Remote Similarity NPC226193
0.5373 Remote Similarity NPC601081
0.5263 Remote Similarity NPC483729
0.5231 Remote Similarity NPC474134

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC73656 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data